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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 145 records · Page 8Linked to original sources

Survival of influenza viruses on environmental surfaces.

To investigate the transmission of influenza viruses via hands and environmental surfaces, the survival of laboratory-grown influenza A and influenza B viruses on various surfaces was studied. Both influenza A and B viruses survived for 24-48 hr on hard, nonporous surfaces such as stainless steel and plastic but survived for less than 8-12 hr on cloth, paper, and tissues. Measurable quantities of influenza A virus were transferred from stainless steel surfaces to hands for 24 hr and from tissues to hands for up to 15 min. Virus survived on hands for up to 5 min after transfer from the environmental surfaces. These observations suggest that the transmission of virus from donors who are shedding large amounts could occur for 2-8 hr via stainless steel surfaces and for a few minutes via paper tissues. Thus, under conditions of heavy environmental contamination, the transmission of influenza virus via fomites may be possible.

Gossypium↗

Effect of the ratio of surface area to volume on the penetration of antibiotics in to extravascular spaces in an in vitro model.

The penetration of cephapirin into extravascular spaces of various volumes and ratios of surface area to volume (SA/V) was studied in an in vitro kinetic model. The SA/V ratio was found to be an important determinant of the kinetics of these spaces. The greater the surface area in relation to the volume of the extravascular space, the more closely its kinetics mimicked those of the intravascular space-that is, the higher the absolute peak concentration of drug achieved in the extravascular space, the greater the peak-to-trough fluctuation and the more quickly the peak concentration of drug was reached. Extravascular spaces with similar SA/V ratios demonstrated similar kinetics. Data from various models of extravascular fluid in humans and animals were reviewed, and the kinetics of these extravascular spaces were also found to be determined, at least in part, by the SA/V ratios of the spaces.

Cephalosporins↗

Assay of netilmicin, using enzyme immunoassay for gentamicin.

A homogenous enzyme immunoassay for the quantitative determination of netilmicin in serum was developed. The procedure utilizes a commercially available assay for gentamicin (EMIT; Syva Co., Palo Alto, Calif.). The method was adapted to a microcentrifugal analyzer, and log-logit regression analysis was performed with a computer. The results of samples assayed by this method correlate well with microbioassay (r2 = 0.985) and radioimmunoassay (r2 = 0.986). This method is not only precise and accurate, but also very rapid and economical and compares favorably to other available methods of netilmicin assay.

Gentamicins↗

Effect of method of administration on extravascular penetration of four antibiotics.

The effect of both method of drug administration and serum protein binding on antibiotic penetration into subcutaneous Visking chambers was studied in rabbits. Ampicillin and oxacillin were administered by either repeated intramuscular injection of 30 mg/kg every 4 h or by constant infusion of 7.5 mg/kg per h for 24 h. Gentamicin was given by intramuscular injection of 4 mg/kg every 4 h for 28 h and by constant infusion of 1 mg/kg per h for 24 h. Amikacin was given by intramuscular injection of 8 mg/kg every 4 h for 12 h and by constant intravenous infusion of 2 mg/kg per h for 12 h. Protein binding to rabbit serum was 73% for oxacillin, 9% for ampicillin, 19% for gentamicin, and 0% for amikacin. Chamber concentrations achieved for oxacillin, gentamicin, and amikacin were not significantly different for constant infusion versus intermittent administration. For ampicillin, chamber concentration was slightly higher by constant infusion than by intermittent administration (P less than 0.02). Fluctuations in drug concentration from peak to trough values in the chambers during the intermittent administration studies were markedly dampened when compared with serum fluctuations. This study demonstrates that whereas steady state is reached more rapidly by intermittent administration, the mean steady-state concentration of an antibiotic achieved at an extravascular site is the same or greater by constant infusion than by intermittent dosing. This is true for highly protein bound antibiotics as well as those with low serum protein binding.

Amikacin↗

High-pressure liquid chromatographic assay of ceftizoxime with an anion-exchange extraction technique.

An anion-exchange extraction method was used in conjunction with high-pressure liquid chromatography for assay of ceftizoxime in 181 serum samples. Comparison of this method with bioassay gave a linear regression line described by Y = 1.11 + 0.98 X, with a correlation coefficient of 0.984. The anion-exchange extraction method is a fast, reliable method of preparing serum samples containing ceftizoxime for assay by liquid chromatography.

Biological Assay↗

Role of serum protein binding and multiple antibiotic doses in the extravascular distribution of ceftizoxime and cefotaxime.

The extravascular penetration of ceftizoxime and cefotaxime was studied in a rabbit subcutaneous Visking chamber model. Four rabbits, implanted with four chambers each, received each drug intramuscularly at a dose of 50 mg/kg every 3 hours for eight doses. Serum drug concentrations were measured after the eighth dose, and extravascular (chamber) concentrations were measured after the first and eighth doses. Cefotaxime (93% bound to rabbit serum proteins) demonstrated a much lower peak chamber-to-peak serum percent penetration after the first dose (20/163 = 13%) than did the less-bound (32%) ceftizoxime (21/52 = 40%, P less than 0.002). Similarly, the ratio of the chamber fluid area under the curve to the serum area under the curve was significantly lower for cefotaxime (15%) than for ceftizoxime (44%, P less than 0.002) after the first dose. Both agents approached equilibrium conditions between the intravascular and extravascular space by the eighth dose, and the ratios of chamber area under the curve to serum area under the curve of cefotaxime (76%) and ceftizoxime (79%) were similar. The peak-to-peak percent penetration of ceftizoxime (54%) was still significantly higher than that of cefotaxime (41%, P less than 0.01), although the chamber concentration of cefotaxime (66.2 micrograms/ml) was considerably higher than that of ceftizoxime (28.2 micrograms/ml). This study illustrates (i) dampened peak-to-trough antibiotic level fluctuation seen at extravascular sites as compared with measured serum concentrations, (ii) the large differences in extravascular penetration between single- and multiple-dose studies, and (iii) the importance of serum protein binding in the delay, but not the prevention, of extravascular drug distribution.

Animals↗

Pharmacokinetics, protein binding, and extravascular distribution of ceftizoxime in normal subjects.

Thirteen normal subjects were given 2, 3, or 4 g of ceftizoxime intravenously in a prospective single-blinded study. Serum and urine concentrations were measured for 48 h. The beta-phase serum half-life ranged from 1.4 to 1.7 h. Approximately 100% of the agent was recovered unchanged in the urine over 48 h. Six of 13 subjects reported subjective complaints consisting of mild dizziness and moderate headache, all of which were transient. One subject also had a minimally elevated serum glutamic oxalacetic transaminase level 1 day after drug administration. Based on serum pharmacokinetics and serum protein binding determined in this investigation, unbound ceftizoxime appeared to distribute with the total body water.

Anti-Bacterial Agents↗

Cleaning and disinfection of fiberoptic endoscopes: evaluation of glutaraldehyde exposure time and forced-air drying.

Several alternative schedules of cleaning and disinfection of flexible fiberoptic endoscopes were evaluated during actual use in paired endoscopy suites. Thorough mechanical cleaning with detergent and alcohol was compared with the same cleaning with the addition of 5-, 10-, or 20-min immersion of the endoscope insertion tube in 2% alkaline glutaraldehyde solution. Endoscopes were cultured quantitatively and qualitatively for aerobic bacteria at three different times relative to procedures: after use, immediately after cleaning alone or cleaning plus disinfection, and after storage unused in a cabinet for 20-72 h. Cleaning plus glutaraldehyde immersion for 5 min significantly reduced bacterial contamination both immediately and after storage when compared with cleaning alone. Results of cleaning plus 10- and 20-min glutaraldehyde immersion were not statistically different from cleaning plus 5-min glutaraldehyde immersion. The addition of forced-air drying following disinfection significantly reduced bacterial contamination following storage when compared with storage without previous drying. Cleaning plus brief (5-20 min) glutaraldehyde immersion significantly reduced bacterial contamination of endoscopes when compared with cleaning alone (p less than 0.001) and, when combined with forced-air drying before storage, resulted in 59/63 (94%) negative endoscope cultures by the methods used in this study. These measures do not ensure sterility, but are superior to mechanical cleaning alone and sufficiently practical to be used routinely without undue interruption of busy endoscopy schedules.

Air↗

Etiologic diagnosis of acute pneumonia in adults: a growing challenge.

For most pneumonia patients, an etiologic diagnosis can be established by proper use of noninvasive methods. Cultures of blood and pleural fluid and serologic titers are the most specific. The clinical history is helpful in distinguishing community- from hospital-acquired pneumonia and in identifying patients who are immunosuppressed or aspiration prone. When noninvasive diagnostic means and initial antibiotic therapy fail, the physician must choose between further empiric treatment and an invasive procedure with its attendant risks. For seriously ill and immunosuppressed patients, the need for an etiologic diagnosis is usually sufficient to justify these risks. The need for invasive diagnostic procedures is likely to increase in the future, necessitating greater knowledge of the relative risks and merits of each procedure on the part of all physicians who treat patients with pneumonia.

Acute Disease↗

Pharmacokinetics, protein binding, and predicted extravascular distribution of moxalactam in normal and renal failure subjects.

Ten normal subjects and ten patients with chronic renal failure requiring hemodialysis were given intravenous infusions of moxalactam ranging from 500 mg to 2 g. Serum and urine concentrations were measured for up to 12 h. Renal failure subjects were given doses both during and between hemodialysis treatments. Protein binding of moxalactam in both normal and uremic serum was determined by ultracentrifugation. The serum half-life in normal subjects was 2.1 and 2.3 h for the 1- and 2-g doses, respectively. The half-life of moxalactam in patients with renal failure was 13.9 h on the 500-mg dose and 13.3 h on the 1.0-g dose. During hemodialysis the serum half-life fell to 4.4 and 5.7 h, respectively. Moxalactam protein binding ranged from 52% in normal serum to 36% in renal failure patient serum. Unbound moxalactam appeared to distribute with the entire body water based on the serum pharmacokinetics and antibiotic serum protein binding determined in this study.

Blood Proteins↗

Determination of tolerance to antibiotic bactericidal activity on Kirby-Bauer susceptibility plates.

A rapid method utilizing Kirby-Bauer susceptibility plates was developed to determine bacterial tolerance to antibiotic bactericidal activity. After completion of initial antibiotic disk susceptibility testing, the disks containing cephalothin, cefazolin, nafcillin, oxacillin, and methicillin were removed and replaced with disks containing a potent beta-lactamase. The plates were reincubated for 18-24 hours and examined for regrowth of organisms within the original zone of inhibition. For 15 of 16 patients who had serious Staphylococcus aureus infections, the method correlated with clinical outcome of antibiotic chemotherapy. Broth dilution tests for bactericidal activity only correlated with clinical response for 11 of 16 patients. One hundred consecutive clinical S. aureus isolates tested with the new method demonstrated tolerance in 27% of strains to cephalothin, 15% to cefazolin, 1% to oxacillin, and 2% of nafcillin.

Anti-Bacterial Agents↗

Evaluation of a commercial microdilution system for quantitative susceptibility testing of aminoglycosides against multidrug-resistant, gram-negative bacilli.

Susceptibility of clinical isolates of Pseudomonas aeruginosa (29 isolates), Klebsiella species (54 isolates), Escherichia coli (28 isolates), Serratia marcescens (28 isolates), and Enterobacter species (29 isolates) to gentamicin, tobramycin, and amikacin was determined by the following three methods: commercial broth microdilution trays, standard agar dilution, and disk diffusion susceptibility. A total of 504 tests were performed by each method, and overall susceptibility or resistance determined by the broth microdilution method agreed with that determined by the agar dilution method in 92.7% of the tests, whereas results from the disk diffusion method agreed with those from the agar dilution method in 91.9% of the tests. The broth microdilution and disk diffusion methods agreed with each other 88.7% of the time. The broth microdilution system results varied from the agar dilution method results by more than one dilution in 121 of 504 determinations (24%); however, this altered susceptibility determinations in only 7.3% of the assays. E. coli isolates were found to be quantitatively more resistant to the aminoglycosides with the broth microdilution method than with the agar dilution method. In contrast, the broth microdilution method demonstrated P. aeruginosa to be quantitatively more susceptible to the aminoglycosides than when the results were obtained by the agar dilution method. The Micro-Media Systems method is economical, reliable, rapid, and simple to perform and yields quantitative minimum inhibitory concentrations.

Aminoglycosides↗

Comparative activities of the oxa-beta-lactam LY127935, cefotaxime, cefoperazone, cefamandole, and ticarcillin against multiply resistant gram-negative bacilli.

A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum beta-lactams, LY127935 (a 1-oxa-beta-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin >/= 8 mug/ml) usually were as susceptible to the three new broad-spectrum beta-lactams as were non-multiply resistant strains. Both Klebsiella pneumoniae and Serratia marcescens, including multiply resistant and non-multiply resistant strains, were most susceptible to the 1-oxa-beta-lactam LY127935 and cefotaxime. P. aeruginosa (both multiply resistant and non-multiply resistant strains) were most susceptible to cefoperazone. All three new beta-lactams were active against non-multiply resistant strains of Escherichia coli, Enterobacter spp., Proteus spp., and Citrobacter spp. Providencia stuartii were most susceptible to cefotaxime and the 1-oxa-beta-lactam LY127935. The three new beta-lactams were all less active against staphylococci (especially methicillin-resistant Staphylococcus aureus) than cephalothin. Streptococcus pyogenes and S. pneumoniae were very susceptible to cefotaxime and cefoperazone, though less susceptible to LY127935. None of the three new beta-lactams was active against S. faecalis. All were very active against both penicillinase-positive and -negative strains of Neisseria gonorrhoeae.

Bacteria↗